All Posts tagged colleagues

Low vitamin D common in lung disease

Kinder and his colleagues assessed the prevalence of vitamin D deficiency in a cohort of patients with interstitial lung disease, who are often treated with corticosteroids. The detrimental effect of chronic use of corticosteroids on bone health has been well established, according to the researchers. Of the patients included in the study, 51 had interstitial lung disease and 67 had other forms of interstitial lung disease related to autoimmune connective tissue diseases.

A vitamin D insufficiency was defined as a serum level of less than 30 ng/mL. A level of less than 20 ng/mL was considered deficient. Both insufficient and deficient levels were prevalent in the study. In the overall sample, lower vitamin D levels were associated with reduced forced vital capacity (P=0.01). When the analysis was restricted to patients with connective tissue disease, both forced vital capacity and diffusing capacity of lung for carbon monoxide — a measure of the lung’s ability to transfer gases from the air to the blood — were significantly reduced (P<0.05 for both). After adjustment for several potential confounders — including age, corticosteroid use, race, and season, the presence of connective lung disease was a strong predictor of vitamin D insufficiency (OR 11.8, 95% CI 3.5 to 40.6).

According to the researchers, a pathogenic role of low vitamin D in the development of autoimmune diseases such as interstitial lung disease is plausible because of the immunoregulatory role of the biologically active form of vitamin D, 1,25-(OH)2D. “All cells of the adaptive immune system express vitamin D receptors and are sensitive to the action of 1,25-(OH)2D,” they wrote. “High levels of 1,25-(OH)2D are potent inhibitors of dendritic cell maturation with lower expression of major histocompatibility complex class II molecules, down-regulation of costimulatory molecules, and lower production of proinflammatory cytokines.” “A common theme in the immunomodulatory functions of vitamin D is that higher levels are immunosuppressive,” they continued, “which is consistent with a potential role for hypovitaminosis D in the pathogenesis of autoimmune disorders.”

In a statement, Len Horovitz, MD, a pulmonary specialist at Lenox Hill Hospital in New York City, commented that “vitamin D is known to promote wound healing, and to benefit the immune system. So it is not surprising to find that patients with immune lung disorders are vitamin D deficient.” He said that all of his patients are screened and treated for vitamin D deficiency with supplements. The study authors noted that further research is needed to determine whether supplementation is associated with improved outcomes. The study was limited, Kinder and his colleagues wrote, by its use of patients from a single center in Cincinnati.

In addition, the cross-sectional design of the study did not evaluate whether vitamin D supplementation is associated with any improved clinical outcomes. To examine that issue, the team called for prospective controlled interventional studies to determine whether vitamin D7 supplements can ameliorate symptoms and improve outcomes in connective tissue disease-related interstitial lung disease.

Source reference: Hagaman J, et al “Vitamin D deficiency and reduced lung function in connective tissue-associated interstitial lung diseases” Chest 2011; DOI: 10.1378/chest.10-0968.

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Why the rise in Multiple Sclerosis

New research may help explain why multiple sclerosis rates have risen sharply in the U.S. and some other countries among women, while rates appear stable in men.The study could also broaden understanding of how environmental influences alter genes to cause a wide range of diseases. The causes of multiple sclerosis (MS) are not well understood, but experts have long suspected that environmental factors trigger the disease in people who are genetically susceptible. In the newly published study, researchers found that women with MS were more likely than men with MS to have a specific genetic mutation that has been linked to the disease.

Women were also more likely to pass the mutation to their daughters than their sons and more likely to share the MS-susceptibility gene with more distant female family members. If genes alone were involved, mothers would pass the MS-related gene to their sons as often as their daughters, said researcher George C. Ebers, MD, of the University of Oxford. Ebers’ research suggests that the ability of environmental factors to alter gene expression — a relatively new field of genetic study known as epigenetics — plays a key role in multiple sclerosis and that this role is gender-specific.

The theory is that environmental influences such as diet, smoking, stress, and even exposure to sunlight can change gene expression and this altered gene expression is passed on for a generation or two. “The idea that the environment would change genes was once thought to be ridiculous,” Ebers says. “Now it is looking like this is a much bigger influence on disease than we ever imagined.”

The study by Ebers and colleagues included 1,055 families with more than one person with MS. Close to 7,100 genes were tested, including around 2,100 from patients with the disease. The researchers were looking for MS-specific alterations in the major histocompatibility complex (MHC) gene region. They found that women with MS were 1.4 times more likely than men with the disease to carry the gene variant linked to disease risk. A total of 919 women and 302 men had the variant in the MHC region, compared to 626 women and 280 men who did not have it.

The study appeared in the Jan. 18 issue of Neurology.

Epigenetics is not evolution. Genetic alterations linked to environmental assaults can be passed down for a generation or two, but DNA usually rights itself over time, Ebers says. “This may explain why we hardly ever see MS in families over more than three generations,” he says. Earlier studies by Ebers and colleagues suggest that vitamin D deficiency may be the environmental stressor that triggers the MS-linked gene alterations. Rates of the disease are highest among people living farthest from the equator, and there is widespread speculation that lack of vitamin D due to low sun exposure may explain this. Other than Ebers’ research team, Orhun Kantarci, MD, of the Mayo Clinic in Rochester, Minn., is one of the few researches studying epigenetics as it relates to multiple sclerosis.

Kantarci calls the new research a potentially important piece of the puzzle to explain the gender difference in MS, but he adds that the research must be replicated. “This study provides more questions than answers, but it is very interesting,” he says. “We are learning that inheritance isn’t as simple as [Gregor] Mendel described.”

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Age related protein linked to cancer

Age related protein linked to cancer

The most common type of breast cancer in older women — estrogen and progesterone receptor (ER/PR) positive breast cancer — has been linked to a protein that fends off aging-related cellular damage. A new study led by Vanderbilt-Ingram Cancer Center researcher David Gius, M.D., Ph.D., now shows how a deficiency in this aging-associated protein may set the stage for these tumors to develop.

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The findings, published in Molecular Cell, provide information that could assist in the screening, prevention and treatment of these common age-related cancers. While the young are certainly not spared cancer’s wrath, cancer is primarily a disease of aging, with the majority of cases occurring in people over 50. However, the biological processes that underlie this association are not clear.

“The connection between aging and cancer is one of the most established phenomena in cancer research,” said Gius, associate professor of Cancer Biology, Pediatrics and Radiation Oncology. “The problem to address this clinically significant question is that this field lacks in vivo models to study this.”

In the late-1990s, proteins called “sirtuins” were linked to extended lifespan observed in several species maintained on a calorically restricted diet. These nutrient-sensing sirtuin proteins seemed to defend against aging-related cellular damage. Sirtuins are present in all living organisms, with humans having seven different sirtuin proteins. “When (the sirtuins) were discovered, it seemed obvious to conclude that there might be a mechanistic connection between the genes that determine length of survival and cancer,” Gius said. Previously, while at the National Cancer Institute, Gius and colleagues created mice lacking some of these sirtuins.

They reported last January in Cancer Cell that when they knocked out Sirt3 — a sirtuin localized in the mitochondria, the cellular “power plants” — the mice developed ER/PR positive breast tumors, the most common type of breast cancer in postmenopausal women. These tumors also exhibited increased levels of damaging free radicals and “reactive oxygen species” (ROS) — including superoxide, the primary metabolite of oxygen in the mitochondria — which provided an important clue as to how Sirt3 deficiency might permit these tumors to develop. “The mechanism, at least in part, for why these mice develop receptor positive breast cancer is altered mitochondrial ROS, including superoxide,” Gius said. But how deficiency in a longevity gene led to increased ROS was not clear. Since superoxide is generally removed from the cell with the help of a detoxifying enzyme called manganese superoxide dismutase (MnSOD), Gius hypothesized that the Sirt3 deficiency may abnormally regulate MnSOD.

In the current study, the researchers show that Sirt3 knockout mice have decreased MnSOD activity despite having normal levels of the protein. Gius and colleagues determined that the MnSOD in Sirt3 knockout mice was abnormally modified (with a chemical “acetyl” group) at a specific amino acid (lysine 122). This aberrant modification of MnSOD reduced the enzyme’s ability to detoxify superoxide and appeared to explain the increase in ROS in Sirt3 knockout mouse tumors. “These results suggest that aberrant regulation of MnSOD plays a role in receptor positive breast cancer,” said Gius.

Gius and colleagues also developed an antibody that can assess the acetylation status of MnSOD, which he says can potentially be used “to screen breast tissue samples to determine what women are at risk for (receptor positive) cancer or for recurrence because of this dysregulation of MnSOD.” Additionally, agents that target the acetylation of this amino acid on MnSOD may be useful as chemopreventive therapies in women at risk of these cancers and of recurrence, he noted. The research was supported by grants from the National Cancer Institute and the Department of Defense.

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Generational risk of diabetes

To test their hypothesis that environmental influences experienced by the father can be passed down to the next generation in the form of changed epigenetic information, Rando and colleagues fed different diets to two groups of male mice. The first group received a standard diet, while the second received a low-protein diet. To control for maternal influences, all females were fed the same, standard diet. Rando and colleagues observed that offspring of the mice fed the low-protein diet exhibited a marked increase in the genes responsible for lipid and cholesterol synthesis in comparison to offspring of the control group fed the standard diet.

These observations are consistent with epidemiological data from two well-known human studies suggesting that parental diet has an effect on the health of offspring. One of these studies, called the Överkalix Cohort Study, conducted among residents of an isolated community in the far northeast of Sweden, found that poor diet during the paternal grandfather’s adolescence increased the risk of diabetes, obesity and cardiovascular disease in second-generation offspring. However, because these studies are retrospective and involve dynamic populations, they are unable to completely account for all social and economic variables. “Our study begins to rule out the possibility that social and economic factors, or differences in the DNA sequence, may be contributing to what we’re seeing,” said Rando. “It strongly implicates epigenetic inheritance as a contributing factor to changes in gene function.”

The results also have implications for our understanding of evolutionary processes, says Hans A. Hofmann, PhD, associate professor of integrative biology at the University of Texas at Austin and a co-author of the study. “It has increasingly become clear in recent years that mothers can endow their offspring with information about the environment, for instance via early experience and maternal factors, and thus make them possibly better adapted to environmental change. Our results show that offspring can inherit such acquired characters even from a parent they have never directly interacted with, which provides a novel mechanism through which natural selection could act in the course of evolution.” Such a process was first proposed by the early evolutionist Jean-Baptiste Lamarck, but then dismissed by 20th century biologists when genetic evidence seemed to provide a sufficient explanation.

Taken together, these studies suggest that a better understanding of the environment experienced by our parents, such as diet, may be a useful clinical tool for assessing disease risk for illnesses, such as diabetes or heart disease. “We often look at a patient’s behavior and their genes to assess risk,” said Rando. “If the patient smokes, they are going to be at an increased risk for cancer. If the family has a long history of heart disease, they might carry a gene that makes them more susceptible to heart disease. But we’re more than just our genes and our behavior. Knowing what environmental factors your parents experienced is also important.”

The next step for Rando and colleagues is to explore how and why this genetic reprogramming is being transmitted from generation to generation. “We don’t know why these genes are being reprogrammed or how, precisely, that information is being passed down to the next generation,” said Rando. “It’s consistent with the idea that when parents go hungry, it’s best for offspring to hoard calories, however, it’s not clear if these changes are advantageous in the context of a low-protein diet.”

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The deadliest diets : 10 year study

Two specific eating patterns increase the risk of death for older adults, a 10-year study finds.Compared to people who ate healthy foods, men and women in their 70s had a 40% higher risk of death if they got most of their calories from high-fat dairy foods or from sweets and desserts. University of Maryland researcher Amy L. Anderson, PhD, and colleagues monitored the eating patterns of 2,582 adults aged 70 to 79. They found that these diets fell into six patterns or clusters.

After adjusting for risk factors such as sex, age, race, education, physical activity, smoking, and total calories, “the High-Fat Dairy Products cluster and the Sweets and Desserts cluster still showed significantly higher risk of mortality than the Healthy Foods cluster,” Anderson and colleagues found.

The six dietary patterns were:

  • Healthy Foods: Higher intake of low-fat dairy products, fruit, whole grains, poultry, fish, and vegetables. Lower intake of meat, fried foods, sweets, high-energy drinks, and added fat.
  • High-Fat Dairy Products: Higher intake of ice cream, cheese, and 2% and whole milk and yogurt. Lower intake of poultry, low-fat dairy products, rice, and pasta.
  • Sweets and Desserts: Higher intake of doughnuts, cake, cookies, pudding, chocolate, and candy. Lower intake of fruit, fish and other seafood, and dark green vegetables.
  • Meat, Fried Foods, and Alcohol: Higher intake of beer, liquor, fried chicken, mayonnaise/salad dressings, high-energy density drinks, nuts, snacks, rice/pasta dishes, and added fat. Lower intake of low-fat dairy products, fiber/bran breakfast cereal, and other breakfast cereal.
  • Breakfast Cereal: Higher intake of fiber/bran and other breakfast cereals (especially the latter). Low intake of nuts, refined grains, dark yellow vegetables, and dark green vegetables.
  • Refined Grains: Higher intake of refined grains (such as pancakes, waffles, breads, muffins, and cooked cereals such as oatmeal) and processed meat (such as bacon, sausage, ham, and other lunchmeats). Lower intake of liquor, breakfast cereals, and whole grains.

Several of the groups got an unusually large amount of their total calories from just one food group:

The sweets and desserts cluster got 25.8% of its total energy from sweets.The refined grains cluster got 24.6% of its total energy from refined grains.The breakfast cereal group got 19.3% of its total energy from cold cereals other than those full of fiber and bran.The high-fat dairy products group got 17.1% of its total energy from higher-fat dairy foods.

Overall, people in the healthy foods cluster had more years of healthy life and a lower death rate than all other groups. Moreover, their blood tests came back with significantly more indicators of health than the other groups.

But not all of the study findings were so predictable. “Unexpectedly, in this and in several other studies, a [dietary] pattern higher in red meat was not significantly associated with increased risk of mortality,” Anderson and colleagues note. It's also not entirely clear why the Meat, Fried Food, and Alcohol cluster didn't have a significantly higher death risk, as most diets warn people to limit or avoid such foods.

“In our study, the Meat, Fried Food, and Alcohol cluster did have a slightly higher percentage of total energy from vegetables, fruit, and whole grains than both the High-Fat Dairy Products and Sweets and Desserts clusters, which showed higher risk of mortality,” Anderson and colleagues suggest.

This was by far the most common eating pattern seen in the study: 27% of participants were in the meat, fried food, and alcohol cluster. But Anderson and colleagues do not recommend such a diet. Instead, they point to the fact that 14.5% of study participants were in the healthy foods cluster. “Adherence to such a diet appears a feasible and realistic recommendation for potentially improved survival and quality of life in the growing older adult population,” Anderson and colleagues conclude.

The study appears in the January 2011 issue of the Journal of the American Dietetic Association.
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A Whey to Reduce High Blood Pressure

Supplementing diet with whey-based protein may help reduce high blood pressure, a U.S. researcher says.

Nutritional biochemist Susan Fluegel of Washington State University in Spokane says daily doses of commonly available whey brought a more than 6-point reduction in the average blood pressure of men and women with elevated systolic and diastolic blood pressures. Whey is a by-product of cheese-making. “One of the things I like about this is it is low-cost,” Fluegel says in a statement. “Not only that, whey protein has not been shown to be harmful in any way.”

The study, published in International Dairy Journal, finds not everyone drinking the whey-supplemented drink has changes in blood pressure.

The supplement did not lower the blood pressure of subjects who did not have elevated pressure to begin with. That's good, says Fluegel, since low blood pressure can also be a problem. However, blood-pressure reductions — as seen in those with elevated pressure in this study — can bring a 35 percent to 40 percent reduction in fatal strokes, says Fluegel.

Fluegel and colleagues looked at 71 student subjects ages 18-26, but Fluegel says older people with blood pressure issues would likely get similar results. The supplement was delivered in fruit-flavored drinks developed at the university's creamery.

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A high fat diet can disrupt our biological clock

To examine this thesis, Froy and his colleagues, Ph.D. student Maayan Barnea and Zecharia Madar, the Karl Bach Professor of Agricultural Biochemistry, tested whether the clock controls the adiponectin signaling pathway in the liver and, if so, how fasting and a high-fat diet affect this control. Adiponectin is secreted from differentiated adipocytes (fat tissue) and is involved in glucose and lipid metabolism. It increases fatty acid oxidation and promotes insulin sensitivity, two highly important factors in maintaining proper metabolism.

The researchers fed mice either a low-fat or a high-fat diet, followed by a fasting day, then measured components of the adiponectin metabolic pathway at various levels of activity. In mice on the low-fat diet, the adiponectin signaling pathway components exhibited normal circadian rhythmicity. Fasting resulted in a phase advance. The high-fat diet resulted in a phase delay. Fasting raised and the high-fat diet reduced adenosine monophosphate-activated protein kinase (AMPK) levels. This protein is involved in fatty acid metabolism, which could be disrupted by the lower levels.

In an article soon to be published by the journal Endocrinology, the researchers suggest that this high-fat diet could contribute to obesity, not only through its high caloric content, but also by disrupting the phases and daily rhythm of clock genes. They contend also that high fat-induced changes in the clock and the adiponectin signaling pathway may help explain the disruption of other clock-controlled systems associated with metabolic disorders, such as blood pressure levels and the sleep/wake cycle.

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Calcium may help you live longer

All had reported on their diet at the beginning of the study. During follow-up, about 2,358 died.

The top calcium consumers had a 25 percent lower risk of dying from any cause and a 23 percent lower risk of dying from heart disease during follow-up relative to men that had the least amount of calcium in their diet. Calcium intake didn't significantly influence the risk of dying from cancer.

Men in the top third based on their calcium intake were getting nearly 2,000 milligrams a day, on average, compared to about 1,000 milligrams for men in the bottom third. The US Recommended Dietary Allowance (RDA) for calcium intake is 1,000 milligrams for men 19 to 50 years old and 1,200 milligrams for men 50 and over. “Intake of calcium above that recommended daily may reduce all-cause mortality,” Kaluza and her colleagues conclude.

Calcium could influence mortality risk in many ways, they note, for example by reducing blood pressure, cholesterol, or blood sugar levels. For the men in the study, the main sources of calcium in the diet were milk and milk products and cereal products. In contrast to calcium, there was no relationship between magnesium consumption and overall mortality or deaths from cancer or heart disease. Study participants' intakes ranged from around 400 milligrams per day to around 525 milligrams; the RDA for magnesium is 420 milligrams for men 31 and older.

This analysis, the researchers say, may have found no effect for magnesium because all of the men in the study seemed to be getting enough of the mineral in their diet. “Further studies are needed in other populations with lower dietary magnesium intakes to address this issue,” they say. Future research should also look into calcium and magnesium intake from drinking water, they add, which can be a significant source of these minerals.

SOURCE: American Journal of Epidemiology

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Vitamin K tied to lower cancer risk

In the current study, vitamin K2 — which study participants most frequently got through cheese — was linked to the odds of developing or dying from cancer, whereas vitamin K1 was not.

The findings are based on data from 24,340 German adults who were between the ages of 35 and 64, and cancer-free at the outset. The researchers estimated the participants' usual vitamin K intake based on a detailed dietary questionnaire. Over the next decade, 1,755 participants were diagnosed with colon, breast, prostate or lung cancers, of whom 458 died during the study period.

In general, the researchers found, the one quarter with the highest intakes of vitamin K2 were 28 percent less likely to have died of any one of the cancers than the one-quarter of men and women with the lowest intakes of the vitamin. That was with factors like age, weight, exercise habits, smoking and consumption of certain other nutrients, like fiber and calcium, taken into account.

Of the one-quarter of study participants who got the least vitamin K2, 156 — or 2.6 percent — died of one of the four cancers. That was true of 1.6 percent of participants with the highest intakes of the vitamin from food.

When Linseisin's team looked at the cancer types individually, there was no clear link between either form of vitamin K and breast cancer or colon cancer. However, greater consumption of vitamin K2 was linked to lower risks of developing or dying from lung cancer — a disease for which smoking is the major risk factor — or of developing prostate cancer.

Of the one-quarter of study participants with the lowest vitamin K2 intakes, 47 — or 0.8 percent — developed lung cancer, versus 0.4 percent of the one-quarter who got the most vitamin K2 in their diets. When it came to prostate cancer, there were 111 cases among the one-quarter of men with the lowest vitamin K2 intakes, and 65 cases in the group with the highest consumption.

In theory, vitamin K itself could offer some protection against cancer. It's often used to counteract too-high doses of blood thinners, although this does not have an obvious link to cancer. In lab research, however, Linseisin and his colleagues point out, the vitamin has been shown to inhibit cancer cell growth and promote apoptosis — a process by which abnormal cells kill themselves off.

But whether vitamin K intake itself is responsible for the lower cancer risks in this study is unclear, according to the researchers. One limitation is that they estimated vitamin K intake based on participants' reported eating habits; most of their vitamin K came from eating cheese, and it's possible, Linseisin and his colleagues note, that some other components of that food are related to cancer risk.

Future studies, the researchers say, should measure people's blood levels of vitamin K and look at the relationship of those levels with cancer risks.

SOURCE: American Journal of Clinical Nutrition

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